PO.TB10.13 · 肿瘤生物学

反应性少突胶质细胞通过CCL5/CCR5介导的胶质瘤干细胞维持促进胶质母细胞瘤进展

Reactive oligodendrocytes promote glioblastoma progression through CCL5/CCR5-mediated glioma stem cell maintenance

编号 6228 展板 9 时间 4/21 02:00–05:00 区域 Section 32 主讲 Jason Moffat, PhD

分会场 Tumor-Neuron Interactions and Neuro-Regulation of Cancer

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Nicholas Mikolajewicz¹, Kui Zhai², Anish Puri², Petar Miletic², Nazanin Tatari², jiarun Wei¹, Neil Savage², Zhi Huang³, Qian Huang³, Seon Yong Lee¹, Mahta Jan-Ahmadnejad⁴, Roseanne Nguyen⁴, David Chen¹, Tiegan Korman², Daniel Mobilio², Maxwell Topley², Jack Qinyu Lu², Matthew R. Voisin², Zsolt Zador², Shawn C. Chafe², Chitra Venugopal², Kevin R. Brown¹, Gelareh Zadeh⁵, Hong Han², Julien Muffat⁴, Shideng Bao³, Sheila K. Singh², Jason Moffat¹

¹Genetics and Genome Biology, Sick Children's Hospital, Toronto, ON, Canada,²McMaster University, Hamilton, ON, Canada,³Cancer Biology, Cleveland Clinic, Cleveland, OH,⁴Neurosciences and Mental Health, Sick Children's Hospital, Toronto, ON, Canada,⁵University Health Network, Toronto, ON, Canada

摘要 Abstract

中文摘要

胶质母细胞瘤(GBM)在富含少突胶质细胞谱系(OL)细胞的微环境中演进。在本研究中,我们利用来自原发性和复发性GBM肿瘤的单细胞和空间转录组学、免疫组织化学、细胞因子谱分析以及迁移实验,证明GBM细胞通过CXC3L1/CXC3R1信号将OL招募至肿瘤边界。一个泛疾病人类OL荟萃图谱以及同基因小鼠模型揭示了一种干扰素诱导的反应性OL状态,类似于在脱髓鞘性炎症及创伤性损伤中所见的状态,该状态在中枢神经系统恶性肿瘤中富集。这些反应性OL分泌促肿瘤发生的细胞因子,尤其是CCL5,可通过CCR5信号促进GBM肿瘤细胞生长。CCR5优先表达于胶质瘤干样细胞(GSC)中,并在复发时上调。通过基因敲低或FDA批准的药物Maraviroc靶向CCR5可损害GSC的干性并延长GBM模型的生存期。我们的工作凸显了OL与GBM细胞之间的功能性相互作用,并将CCL5/CCR5轴确立为GBM中一个可成药的靶点。

查看英文原文 English abstract

Glioblastoma (GBM) evolves within a microenvironment abundant in oligodendrocyte-lineage (OL) cells. In this study, we utilized single-cell and spatial transcriptomics from primary and recurrent GBM tumors, immunohistochemistry, cytokine profiling, and migration assays to show that GBM cells recruit OLs to the tumor border via CXC3L1/CXC3R1 signaling. A pan-disease human OL meta-atlas and syngeneic mouse models reveal an interferon-induced reactive OL state, akin to those seen in demyelinating inflammatory and traumatic injury, which is enriched in CNS malignancies. These reactive OLs secrete pro-tumorigenic cytokines, notably CCL5, that promote GBM tumor cell growth through CCR5 signaling. CCR5 is preferentially expressed in glioma stem-like cells (GSCs) and upregulated at recurrence. Targeting CCR5 with genetic knockdown or FDA-approved drug Maraviroc impairs GSC stemness and prolongs survival in GBM models. Our work highlights the functional interplay between OLs and GBM cells and positions the CCL5/CCR5 axis as a druggable target in GBM.

利益披露 Disclosure

N. Mikolajewicz, None.. K. Zhai, None.. A. Puri, None.. P. Miletic, None.. N. Tatari, None.. J. Wei, None.. Z. Huang, None.. Q. Huang, None.. S. Lee, None.. M. Jan-Ahmadnejad, None.. R. Nguyen, None.. D. Chen, None.. T. Korman, None.. D. Mobilio, None.. M. Topley, None.. J. Lu, None.. M. R. Voisin, None.. Z. Zador, None.. S. C. Chafe, None.. C. Venugopal, None.. K. R. Brown, None.. G. Zadeh, None.. H. Han, None.. J. Muffat, None.. S. Bao, None.. S. K. Singh, None.. J. Moffat, None.

← 返回 AACR 2026 检索